Preparation of aralkanoic acids and esters using mixed ligand catalyst

ABSTRACT

The activity of a palladium catalyst in the carboxylation of an aralkene with carbon monoxide and water or an alcohol in the absence of oxygen can be enhanced when it is used in conjunction with (A) a ligand mixture comprising compounds corresponding to the formulas R 3  ZY and R&#39; 3  Z wherein each R and R&#39; is independently selected from alkyl, aryl and substituted aryl groups; Y is a member of Group VIA of the Periodic Table; and Z is an element having a Pauling electronegativity of 1.9-2.5 or (B) a complex ligand providing all of the elements of said mixture. The invention has particular utility in carboxylating an aralkene such as 4-isobutylstyrene or 2-methoxy-6-vinylnaphthalene to ibuprofen or naproxen or their esters; and the preferred novel ligand is usually a 50/50 mixture of phosphine and phosphine oxide.

This application is a continuation-in-part of application Ser. No.186,933, filed Jan. 27, 1994, now U.S. Pat. No. 5,482,596.

FIELD OF THE INVENTION

The invention relates to a process for preparing aralkanoic acids and,more particularly, relates to such a process employing a novel catalystsystem.

BACKGROUND

As disclosed, e.g., in U.S. Pat. No. 4,694,100 (Shimizu et al.) andBritish Patent 1,565,235 (Mitsubishi), it is known that aralkenes, suchas 4-isobutylstyrene, can be carboxylated with carbon monoxide and wateror an alcohol in the presence of a palladium catalyst under acidicconditions to form an aralkanoic acid or ester, such as ibuprofen.Alperetal., J. Chem. Soc. Chem. Comm., 1983, pp. 1270-1271, disclose asimilar reaction employing a mixture of palladium and copper andrequiring the presence of oxygen; and European Patent Application284,310 (Hoechst Celanese) teaches the use of a palladium catalyst inassociation with a phosphine ligand to accomplish the carboxylation of1-(4-isobutylphenyl)ethanol to ibuprofen with carbon monoxide in anaqueous acidic medium.

These known processes have been used with some success. However, itwould be desirable to develop a process that would not require thepresence of oxygen or an acidic medium or the use of an uneconomicalstarting material like 1-(4-isobutylphenyl)ethanol but would stillprovide the acid or ester product in good yield.

SUMMARY OF THE INVENTION

It has been found that the activity of a palladium catalyst in thecarboxylation of an aralkene with carbon monoxide and water or analcohol in the absence of oxygen can be enhanced when it is used inconjunction with (A) a ligand mixture comprising compounds correspondingto the formulas R₃ ZY and R'₃ Z wherein each R and R' is independentlyselected from alkyl, aryl, and substituted aryl groups; Y is a member ofGroup VIA of the Periodic Table; and Z is an element having a Paulingelectronegativity of 1.9-2.5 or (B) a complex ligand providing all ofthe elements of said mixture.

Thus, in the process of the invention, an aralkanoic acid or estercorresponding to the formula CH(R³)(R⁴)--C(R²)(Ar)--COOR¹ is prepared bytreating an aralkene having the formula C(R³)(R⁴)═C(R²)Ar and a compoundof the formula R¹ OH with carbon monoxide at a temperature of 25-200° C.and a pressure of at least ˜1 atmosphere (˜0.1 MPa) in the absence ofoxygen and in the presence of a palladium catalyst mixture containing acombination of R₃ ZY and R'₃ Z ligand elements;

R and R' in the above formulas being independently selected from alkyl,aryl, and substituted aryl groups; Y being a member of Group VIA of thePeriodic Table; Z being an element having a Pauling electronegativity of1.9-2.5; R¹ being hydrogen or alkyl; R², R³, and R⁴ being independentlyselected from hydrogen, alkyl, halo, trifluoromethyl, alkoxy, alkylthio,alkanoyl, cycloalkyl-substituted alkyl, cycloalkyl, substituted orunsubstituted aryl or heteroaryl, and substituted or unsubstituted aroylor heteroarylcarbonyl groups; and Ar being substituted or unsubstitutedaryl.

DETAILED DESCRIPTION

Aralkenes that may be carboxylated in the practice of the invention maybe any of those indicated above.

Alkyl substituents in these compounds may have straight or branchedchains and contain 1-20 carbons, such as methyl, ethyl, propyl, butyl,isobutyl, sec-butyl, t-butyl, pentyl, hexyl, octyl, 2-ethylhexyl,1,1,3,3-tetramethylbutyl, decyl, tetradecyl, eicosyl, etc., whilecycloalkyl groups contain 3-7 carbons (e.g., cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, and cycloheptyl), and cycloalkyl-substitutedalkyl groups have a cycloalkyl moiety of 3-7 carbons and a straight- orbranched-chain alkyl moiety of 1-8 carbons, as in cyclopropylmethyl,cyclobutylmethyl, cycloheptylmethyl, 2-cyclopropylethyl,2-cyclohexylethyl, 3-cyclopentylpropyl, 4-cyclopropylbutyl,6-cyclohexylhexyl, and the like. When present, alkoxy and alkylthiosubstituents may be straight- or branched-chain groups containing 1-10carbons (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy,t-butoxy, hexyloxy, octyloxy, decyloxy, methylthio, ethylthio,propylthio, butylthio, pentylthio, hexylthio, octylthio, etc.); and anyalkanoyl groups have 2-18 carbons, as in acetyl, propionyl, butyryl,isobutyryl, pivalolyl, valeryl, hexanoyl, octanoyl, lauroyl, andstearoyl groups, etc.

Both the essential aryl substituent and any optional aryl substituentsin the aralkenes may be phenyl or naphthyl groups that are unsubstitutedor that bear one or more substituents selected from halo (chloro, bromo,fluoro, or iodo), amino, nitro, hydroxy, alkyl, alkoxy, aryloxy(including phenoxy and phenoxy substituted with halo, alkyl, alkoxy, andthe like), and haloalkyl having a straight or branched chain of 1-8carbons bearing at least one halo substituent (including, e.g.,chloromethyl, bromomethyl, fluoromethyl, iodomethyl, 2-chloroethyl,3-bromopropyl, 4-fluorobutyl, dichloromethyl, dibromomethyl,2,2-difluoroethyl, 3,3-dichloropropyl, 4,4-dichlorobutyl,trichloromethyl, trifluoromethyl, 2,2,2-trifluoroethyl,2,3,3-trifluoropropyl, 1,1,2,2-tetrafluoroethyl, etc.). Any aroylsubstitutents in the aralkenes are aroyl groups corresponding to theabove aryl groups, i.e., benzoyl or naphthoyl groups that areunsubstituted or that bear one or more of the substituents listed above.

When the aralkene includes a substituted or unsubstituted heteroarylgroup, that group has a 5-10 membered mono- or fused-heteroaromatic ringcontaining at least one heteroatom selected from nitrogen, oxygen, andsulfur (e.g., 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl,3-pyridyl, 4-pyridyl, pyrazolyl, imidazolyl, pyrimidinyl, pyridazinyl,pyrazinyl, benzimidazolyl, quinolyl, oxazolyl, thiazolyl, indolyl, etc.)and may bear one or more substituents selected from halo, amino, nitro,hydroxy, alkyl, alkoxy, and haloalkyl on the ring. Anyheteroarylcarbonyl substitutents in the aralkenes are heteroarylcarbonylgroups corresponding to the above heteroaryl groups, e.g., furoyl,thienoyl, nicotinoyl, isonicotinoyl, pyrazolylcarbonyl,imidazolylcarbonyl, pyrimidinylcarbonyl, and benzimidazolylcarbonylgroups that are unsubstituted or that bear one or more of thesubstituents listed above.

The preferred aralkene starting materials are compounds in which Ar issubstituted or unsubstituted aryl; and R², R³, and R⁴ representhydrogen, C₁ -C₂ alkyl, trifluoromethyl, or substituted or unsubstitutedphenyl. More preferably, Ar is alkylphenyl or alkoxynaphthyl; and R²,R³, and R⁴ are hydrogen, methyl, or trifluoromethyl.

The R¹ OH hydroxyl compound with which the aralkene is reacted isordinarily water or an alkanol in which R¹ represents a linear orbranched chain of 1-8 carbons, as in methanol, ethanol, propanol,isopropyl alcohol, n-, iso-, sec-, and t-butyl alcohols, the pentanols,the hexanols, the octanols, etc.--methanol and ethanol, especiallyethanol, being preferred when an ester product is sought. However, otheralcohols, glycols, aromatic hydroxy compounds, and other sources ofalkoxy ions e.g., compounds corresponding to the formulas HC(OR¹)₃, R⁵ ₂C(OR¹)₂, HCOOR¹, B(OR¹)₃, Ti(OR¹)₄, and Al(OR¹)₃, wherein R¹ is aspreviously defined and R⁵ is hydrogen or any of the groups defined by R¹! can be used as alternatives to these alkanols if desired.

The amount of R¹ OH employed in the reaction should be at least ˜1 molper mol of aralkene, and it is usually preferred to use an excess of thehydroxyl compound to assist in driving the reaction to completion. Infact, the hydroxyl compound can be used in as high an amount as the sizeof the reaction vessel permits, and particularly large amounts are aptto be desirable to serve the additional function of reaction medium whenno other reaction medium is utilized. However, controlling the amount ofhydroxyl compound is advantageous in producing the highest yields ofproduct, so it is normally preferred to employ ˜2-50, more preferably˜3-24, mols of hydroxyl compound per mol of aralkene reactant.

As already indicated, the amount of carbon monoxide used in the processof the invention should be enough to provide a partial pressure of atleast ˜1 atmosphere (˜0.1 MPa) in the reaction vessel, and higherpressures up to the pressure limits of the reaction vessel can beutilized. Pressures up to ˜3000 psig (˜20.7 MPa) are convenient toemploy. Preferably, the pressure is ˜100-3000 psig (˜0.7-20.7 MPa), morepreferably ˜200-800 psig (˜1.4-5.5 MPa). Since the presence of oxygen isundesirable in the practice of the invention, it is most preferable toconduct the reaction in an atmosphere of 100% carbon monoxide. However,part of this atmosphere can be replaced by one or more inert gases, suchas nitrogen, argon, etc., as long as the reaction is not slowed to thepoint of necessitating exceptionally long periods for completing thereaction.

The process of the invention is usually conducted at a temperature of25-200° C., preferably 25-120° C., and most preferably 50-100° C.,although higher temperatures can also be used. A small advantage inyield can be obtained by gradually increasing the temperature within thepreferred ranges during the course of the reaction.

As already indicated, an acidic medium is not required for the processof the invention, and it is sometimes preferred to conduct the reactionin the absence of any added acid. However, acid may be added in gaseousor liquid form when its presence is desired. When added acid isutilized, it may be an acid such as sulfuric, phosphoric, or sulfonicacid but is preferably a hydrogen halide, especially hydrogen chlorideor hydrogen bromide; and it is usually employed in an amount such as toprovide up to 40 mols, preferably up to 10 mols, and more preferably upto ˜4 mols of H⁺ per mol of aralkene reactant.

In the processes conducted to form ester products, it can be importantto add any acid in gaseous or other non-aqueous form (e.g., as analcoholic solution) when it is desired to maintain anhydrous conditionsin order to avoid the formation of an acid by-product. However, in thesyntheses of acid products, as well as in the ester syntheses when somecontamination with acid by-products is tolerable, an acid added to thereaction mixture may alternatively be incorporated in the form of anaqueous solution, e.g., the common hydrochloric and hydrobromic acidsolutions. Hydrochloric acid is frequently preferred, especiallyhydrochloric acid having a concentration of ˜10-30%.

Except for its ligand component, the palladium catalyst system of theinvention is conventional. Thus, it comprises a reaction-promotingquantity of palladium metal and/or a palladium salt (e.g., palladium(II)chloride, bromide, nitrate, sulfate, or acetate), optionally inconjunction with one or more copper salts (such as copper(II) chloride,bromide, nitrate, sulfate, or acetate), as well as the inventivecombination of R₃ ZY and R'₃ Z ligand elements; and the palladiumcomponent(s) and any copper component(s) may be unsupported or supportedon, e.g., carbon, silica, alumina, zeolite, clay, or a polymericmaterial to provide a heterogeneous catalyst.

The novel ligand component of the catalyst system is a combination of R₃ZY and R'₃ Z ligand elements wherein Z is an element having a Paulingelectronegativity of 1.9-2.5 (e.g., sulfur, nitrogen, osmium,phosphorus, arsenic, antimony, mercury, tellurium, germanium, orbismuth), Y is a member of Group VIA of the Periodic Table (usuallyoxygen, sulfur, or selenium), and each R and R' is independentlyselected from alkyl, aryl, and substituted aryl groups or is joinedtogether with the other Rs or R's and Z to form a heteroaromatic ring,e.g., pyridine, thiopyran, etc.

It is frequently preferred for each of the Rs and R's to be separate andidentical C₁ -C₆ alkyl, phenyl, or substituted phenyl groups (mostpreferably phenyl) and Z to be phosphorus. Also, although thecombination of R₃ ZY and R'₃ Z ligand elements can be provided by usinga single compound combining those elements (e.g.,1,3-bis(diphenylphosphino)propane monoxide, which has the required R₃ Z,R'₃ Z, and Z-Y), it is usually preferred for the ligand to be a mixtureof separate R₃ ZY and R'₃ Z compounds, such as triphenylphosphineoxide/triphenyl phosphine, cyclohexyldiphenylphosphineoxide/cyclohexyldiphenylphosphine,triphenylphosphineoxide/cyclohexyldiphenylphosphine, andethyldiphenylphosphine oxide/ethyldiphenylphosphine mixtures, etc. Whena ligand mixture is used, the R₃ ZY/R'₃ Z ratio may vary from 1/99 to99/1. However, it is preferably in the range of 80/20 to 20/80, morepreferably 60/40 to 40/60; and it is most preferable for the ligandmixture to be composed of substantially equal parts of the two ligands.

The ligand component of the catalyst mixture is used in an amount suchas to provide at least one mol, preferably ˜2-40 mols, and morepreferably 2-20 mols of ligand per mol of the palladium and any coppercomponents. The amount of palladium and optional copper components ispreferably such as to provide ˜4-8000, more preferably ˜10-4000, andmost preferably ˜20-2000 mols of aralkene reactant per mol of thesemetal components.

Although some or all of the components of the catalyst mixture can bepremixed before they are added to the reaction vessel, it is usuallypreferred to add the components(e.g., palladium(II) chloride, copper(II)chloride, and a ligand mixture of triphenylphosphine andtriphenylphosphine oxide) individually, either simultaneously orsequentially.

It is not necessary to employ a solvent in the process of the invention,since an excess of the hydroxyl reactant can be used to serve as areaction medium. However, it is sometimes desirable to employ one ormore solvents such as an alcohol different from the hydroxyl reactant(e.g., methanol, ethanol, a propanol, a butanol, a hexanol, etc.); anacid or ester, such as formic or acetic acid or ethyl acetate; anaromatic hydrocarbon, such as toluene, ethylbenzene, xylenes, and thelike; a ketone, such as acetone, methyl ethyl ketone, diethyl ketone,methyl n-propyl ketone, acetophenone, etc.; or a linear, poly, or cyclicether, such as diethyl ether, di-n-propyl ether, di-n-butyl ether, ethyln-propyl ether, glyme (the dimethyl ether of ethylene glycol), diglyme(the dimethyl ether of diethylene glycol), tetrahydrofuran, dioxane,1,3-dioxolane, etc.

Since some of these solvents (e.g., the alcohols, acids, and esters) arereactive in the process, they should be employed only when theby-product formation consequent from their use can be tolerated. Thus,the solvents which are at least relatively inert under the reactionconditions are apt to be preferred. Ketones such as methyl ethyl ketoneare generally preferred when it is important to minimize by-productformation, although ethers, especially tetrahydrofuran, can be used withsatisfactory results, particularly when the process is not conductedunder acidic conditions.

When employed, the solvent may be used in an amount up to ˜100 mL pergram of aralkene reactant. However, the process is most advantageouslyconducted in the presence of ˜1-30 mL of solvent per gram of aralkene.

The process of the invention leads to the formation of an acid (such asibuprofen or naproxen when the aralkene is, respectively,4-isobutylstyrene or 2-methoxy-6-vinylnaphthalene) when the hydroxylreactant is water, an ester when the aralkene is reacted with an alcoholunder anhydrous conditions, or a mixture of acid and ester when bothwater and an alcohol are used together with the aralkene. When an esteris formed by the process, it canbe conveniently converted to the acid byconventional hydrolysis techniques.

The following examples are given to illustrate the invention and are notintended as a limitation thereof. Abbreviations used therein andpossibly needing definition are shown in the table below.

    ______________________________________    Definitions Table    ______________________________________    Me                methyl    Et                ethyl    Cy                cyclohexyl    Ph                phenyl    MEK               methyl ethyl ketone    THF               tetrahydrofuran    GC                gas chromatography    ______________________________________

EXAMPLE 1 Part A (Comparative)

Charge a 100-mL Hastelloy B autoclave with 0.029 g (0.16 mmol) of PdCl₂and 0. 13 g (0.50 mmol) of triphenylphosphine. Purge the autoclave threetimes with 500 psig (3.45 MPa) of CO, and add a solution of 1.28 g (8.0mmol) of 4-isobutylstyrene, 1.0 mL of water, and 30 mL of THF. Purge theautoclave two more times with 500 psig (3.45 MPa) of CO, and then fillit with CO so as to provide a pressure of 500 psig (3.45 MPa). Agitatethe mixture at 50° C. and monitor the reaction by GC periodically. Theresults of the analyses are shown in Table I.

Part B (Comparative)

Essentially repeat Part A except for replacing the triphenylphosphinewith 0. 15 g (0.54 mmol) of triphenylphosphine oxide. After 24 hours at50° C., GC analyses show that no reaction has occurred.

Part C

Essentially repeat Part A except for replacing the triphenylphosphinewith 0. 14 g (0.53 mmol) of Ph₃ P/Ph₃ PO (85/15). The reaction resultsin the formation of ibroprofen (branched product) and3-(4-isobutylphenyl)propionic acid (linear product) in a 98/2 ratio. Theresults of the GC analyses are shown in Table I.

Part D

Essentially repeat Part C except for using a 50/50 Ph₃ P/Ph₃ PO mixtureinstead of the 85/15 mixture. The ibuprofen product has abranched/linear ratio of 100/0. The results of the GC analyses are shownin Table I.

Part E

Essentially repeat Part A except for replacing the triphenylphosphinewith 0. 14 g (0.50 mmol) of Ph₃ P/Ph₃ PS (50/50). The branched/linearratio in the ibuprofen product is 100/0. Results of the GC analyses areshown in Table I.

Part F

Essentially repeat Part A except for replacing the triphenylphosphinewith a mixture of 0.065 g (0.25 mmol) of Ph₃ P and 0.085 g (0.25 mmol)of Ph₃ PSe. The branched/linear ratio in the ibuprofen product is˜200/1. Results of the GC analyses are shown in Table I.

                  TABLE I    ______________________________________    Reaction Rates Using Ph.sub.3 P, Ph.sub.3 PO, Ph.sub.3 P/Ph.sub.3 PO,    Ph.sub.3 P/Ph.sub.3 PS, or Ph.sub.3 P/Ph.sub.3 PSe    % Conversion to Product    Hours  Ex. 1-A Ex. 1-B Ex. 1-C                                  Ex. 1-D                                        Ex. 1-E                                              Ex. 1-F    ______________________________________    2       3      0        8     34    21     8    3      --      0       --     50    --    --    4       9      0       17     60    41    12    5      --      0       --     69    --    --    6      11      0       24     77    53    21    8      16      0       32     89    65    26    10     19      0       40     95    76    31    22     --      0       77     --    --    --    23     --      0       --     100   97    --    24     --      0       --     --    --    --    46     --      --      98     --    --    --    70     --      --      --     --    --    73    ______________________________________

EXAMPLE 2 Part A (Comparative)

Essentially repeat Example 1, Part A, except for replacing thetriphenylphosphine with 0. 13 g (0.50 mmol) of CyPh₂ P. The ibuprofenproduct has a branched/linear ratio of ˜250/1. The results of the GCanalyses are shown in Table II.

Part B

Essentially repeat Part A except for replacing the CyPh₂ P with 0.14 g(0.53 mmol) of CyPh₂ P/CyPh₂ PO (85/15). The results of the GC analysesare shown in Table II.

Part C

Essentially repeat Part B except for using a 50/50 CyPh₂ P/CyPh₂ POmixture instead of the 85/15 mixture. The ibuprofen product has abranched/linear ratio of 100/0. The results of the GC analyses are shownin Table II.

                  TABLE II    ______________________________________    Reaction Rates Using CyPh.sub.2 P or CyPh.sub.2 P/CyPh.sub.2 PO           % Conversion to Product    Hours    Ex. 2-A       Ex. 2-B Ex. 2-C    ______________________________________    2        2             3       38    4        5             8       64    6        8             13      84    7        --            --      91    8        14            19      96    10       18            24      100    22       --            53      --    24       42            --      --    48       78            --      --    ______________________________________

EXAMPLE 3 Part A (Comparative)

Essentially repeat Example 1, Part A, except for replacing thetriphenylphosphine with 0.11 g (0.49 mmol) of EtPh₂ P. No reactionoccurs in 8 hours at 50° C. Raise the temperature to 90° C. and agitatewhile monitoring by GC. GC analyses show 59% conversion after 14 hoursat the higher temperature and 79% conversion after 21 hours at thattemperature. The ibuprofen product has a branched/linear ratio of 68/32.

Part B

Essentially repeat Part A except for using as the ligand a mixture of0.053 g (0.25 mmol) of EtPh₂ P and 0.057 g (0.25 mmol) of EtPh₂ PO. Asin Part A, no reaction occurs in 8 hours at 50° C., but completeconversion is achieved in only 14 hours at 90° C. The ibuprofen producthas a branched/linear ratio of 88/12.

EXAMPLE 4 Part A (Comparative)

Essentially repeat Example I, Part A, except for replacing the 1 mL ofwater with 1 mL of 10% aqueous HCl. The ibuprofen product has abranched/linear ratio of 98/2. The results of the GC analyses are shownin Table III.

Part B

Essentially repeat Example I, Part D, except for replacing the 1 mL ofwater with 1 mL of 10% aqueous HCl. The ibuprofen product has abranched/linear ratio of 100/0. The results of the GC analyses are shownin Table III.

                  TABLE III    ______________________________________    Reaction Rates Using Acid and    Ph.sub.3 P or Ph.sub.3 P/Ph.sub.3 PO                  % Conversion to Product    Hours           Ex. 4-A Ex. 4-B    ______________________________________    2               8       54    3               --      74    4               20      91    5               --      100    6               34      --    8               45      --    10              56      --    20              100     --    ______________________________________

EXAMPLE 5 Part A (Comparative)

Essentially repeat Example 4, Part A, except for also including 0.05 g(0.37 mmol) of CuCl₂ in the initial charge to the autoclave. Thereaction results in the formation of ibuprofen containing no linearproduct. The results of the GC analyses are shown in Table IV.

Part B

Repeat Part A except for replacing the Ph₃ P ligand with 0.14 g (0.51mmol) of Ph₃ P/Ph₃ PO (85/15). As in Part A, the reaction results in theformation of ibuprofen containing no linear product. The results of theGC analyses are shown in Table IV.

                  TABLE IV    ______________________________________    Reaction Rates Using Cu, Acid, and    Ph.sub.3 P or Ph.sub.3 P/Ph.sub.3 PO                  % Conversion to Product    Hours           Ex. 5-A Ex. 5-B    ______________________________________    2               36      48    4               72      88    5               --      100    6               100     --    ______________________________________

EXAMPLE 6 Part A (Comparative)

Essentially repeat Example 1, Part A, except for replacing the water andTHF with 1 mL of MeOH and 30 mL of MEK, respectively, and also including0.05 g (0.37 mmol) of CuCl₂ in the initial charge to the autoclave. Thereaction results in the formation of methyl2-(4-isobutylphenyl)propionate (branched product) and methyl3-(4-isobutylphenyl)propionate (linear product) in a 98/2 ratio. Resultsof the GC analyses are shown in Table V.

Part B

Essentially repeat Part A except for (1) not replacing the THF with MEKand (2) using, in addition to the triphenylphosphine, 0.14 g (0.49 mmol)of Ph₃ PO. Table V shows the results of the GC analyses conducted up tothe stage of 100% conversion to the ibuprofen ester product having abranched/linear ratio of ˜200/1.

Cool the reactor to room temperature, release CO pressure, add 20 mL ofwater, and extract the product with hexane (3×50 mL). Dry the combinedhexane extracts with MgSO₄, concentrate by rotary evaporation, andchromatograph the resulting residue on a short column (silica gel,eluted with hexanes and 5/1 hexanes/ethyl acetate) to give 1.56 g (89%)of a colorless liquid.

                  TABLE V    ______________________________________    Reaction Rates Using Cu and    Ph.sub.3 P or Ph.sub.3 P/Ph.sub.3 PO                  % Conversion to Product    Hours           Ex. 6-A Ex. 6-B    ______________________________________    2               2       14    4               23      41    6               51      73    8               73      92    10              --      100    22              100     --    ______________________________________

EXAMPLE 7 Part A (Comparative)

Essentially repeat Example 6, Part A, except for employing no CuCl₂ inthe reaction. The ester product has a branched/linear ratio of 97/3.Results of the GC analyses are shown in Table VI.

Part B

Repeat Part A except for replacing the triphenylphosphine ligand with0.13 g (0.50 mmol) of Ph₃ P/Ph₃ PO (50/50). The ester product has abranched/linear ratio of ˜200/1. Results of the GC analyses are shown inTable VI.

                  TABLE VI    ______________________________________    Reaction Rates Using Ph.sub.3 P or Ph.sub.3 P/Ph.sub.3 PO                  % Conversion to Product    Hours           Ex. 7-A Ex. 7-B    ______________________________________    2               0       9    4               2       26    6               6       42    8               11      58    22              76      --    23              --      99    ______________________________________

The preceding examples demonstrate the unexpected improvements inreaction rate and product branched/linear ratio attained when mixturesof R₃ ZY and R'₃ Z ligands are used in the acid and ester synthesesinstead of conventional single ligands. The following example shows thatsimilar results are observed when the R₃ ZY and R'₃ Z ligand elements ofthe novel mixtures are present in a single compound.

EXAMPLE 8 Part A (Comparative)

Essentially repeat Example 1, Part A, except for replacing thetriphenylphosphine with 0.075 g (0.17 mmol) of1,3-bis(diphenylphosphino)propane. No reaction occurs in 21 hours at 50°C. Raise the temperature to 80° C. and agitate while monitoring by GC.The product branched/linear ratio is 32/68. Results of the GC analysesare shown in Table VII.

Part B

Essentially repeat Example 1, Part A, except for replacing thetriphenylphosphine with 0.077 g (0.18 mmol) of1,3-bis(diphenylphosphino)propane monoxide. The branched/linear ratio is100/0. Results of the GC analyses are shown in Table VII.

Part C

Essentially repeat Part B except for conducting the reaction at 80° C.instead of 50° C. The branched/linear ratio is 98/2. Results of the GCanalyses are shown in Table VII.

                  TABLE VII    ______________________________________    Reaction Rates Using 1,3-bis(diphenylphosphino)propane or    1,3-bis(diphenylphosphino)propane monoxide           % Conversion to Product    Hours    Ex. 8-A.sup.1                          Ex. 8-B.sup.2                                   Ex. 8-C.sup.1    ______________________________________    2        12           7        78    3        16           --       92    4        20           13       95    6        25           22       98    8        --           27       --    9        30           --       --    10       --           34       --    23       --           68       --    ______________________________________     .sup.1 Reaction at 80° C.     .sup.2 Reaction at 50° C.

I claim:
 1. A process for preparing an aralkanoic acid corresponding tothe formula CH(R³)(R⁴)--C(R²)(Ar)--COOH by reacting an aralkene havingthe formula C(R³)(R⁴)═C--(R²)Ar with water and carbon monoxide at atemperature of 25-200° C. and a pressure of at least 1 atmosphere (0.1MPa) in the absence of oxygen and in the presence of a palladiumcatalyst mixture containing a ligand; characterized in that the ligandcomprises a combination of R₃ ZY and R'₃ Z ligand elements;each R and R'in the above formulas being (a) independently selected from alkyl, aryl,and substituted aryl groups or (b) joined with the other Rs and R's andthe Z in the same formula to form a heteroaromatic ring; Y representingoxygen, sulfur, or selenium; Z represents an element having a paulingelectronegativity of 1.9-2.5; R², R³, and R⁴ being independentlyselected from hydrogen, alkyl, halo, trifluoromethyl, alkoxy, alkylthio,alkanoyl, cycloalkylsubstituted alkyl, cycloalkyl, substituted orunsubstituted aryl or heteroaryl, and substituted or unsubstituted aroylor heteroarylcarbonyl groups; and Ar being substituted or unsubstitutedaryl.
 2. The process of claim 1 wherein the palladium catalyst mixturecomprises palladium(0) and/or one or more salts of palladium, optionallyin conjunction with one or more copper salts, in addition to thecombination of R₃ ZY and R'₃ Z ligand elements.
 3. The process of claim1 wherein the combination of R₃ ZY and R'₃ Z ligand elements is providedby separate R₃ ZY and R'₃ Z ligands.
 4. The process of claim 3 whereinthe R₃ ZY and R'₃ Z ligands are triphenylphosphine oxide andtriphenylphosphine.
 5. The process of claim 1 wherein the combination ofR₃ ZY and R'₃ Z ligand elements is provided in a single ligand.
 6. Theprocess of claim 1 conducted in a reaction medium.
 7. The process ofclaim 6 wherein the reaction medium is tetrahydrofuran.
 8. The processof claim 6 wherein the reaction medium is methyl ethyl ketone.
 9. Theprocess of claim 1 wherein an aralkene selected from 4-isobutylstyreneand 2-methoxy-6-vinylnaphthalene is reacted with carbon monoxide andwater in the presence of a palladium catalyst mixture comprising apalladium salt, a mixture of triphenylphosphine and triphenylphosphineoxide ligands, and optionally also a copper salt.